RATIONALE: Drugs used in chemotherapy, such as topotecan, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing.

PURPOSE: This phase I trial is studying the side effects, best way to give, and best dose of topotecan when given by intraventricular infusion in treating young patients with neoplastic meningitis due to leukemia, lymphoma, or solid tumors.

Further study details as provided by Pediatric Brain Tumor Consortium:

Primary Outcome Measures:

Estimate the maximum tolerated dose of intraventricular topotecan on this schedule [ Time Frame: First 14 days of therapy ] [ Designated as safety issue: Yes ]

Number of patients with dose-limiting toxicity [ Time Frame: First 14 days of therapy ] [ Designated as safety issue: Yes ]

Estimate the dose of intraventricular topotecan that will result in cerebrospinal fluid lactone concentrations exceeding 1 ng/mL for at least 8 hours after an intrathecal injection [ Time Frame: Day 1 of Week 1 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Number of patients with objective documentation of tumor response to intraventricular topotecan [ Time Frame: Weeks 5, 11 and then every 12 weeks until off study ] [ Designated as safety issue: No ]

MRI of the brain and spine is obtained pre-consolidation, pre-maintenance, and then every 12 weeks in maintenance.

The cerebrospinal fluid (CSF) concentration-time profile for topotecan after intrathecal CSF administration will be modeled from the CSF samples collected on day 1 of week 1. Individual pharmacokinetic parameters estimated will include volume of central compartment, elimination rate constant, half-life, and clearance.

Correlation of imaging parameters with tumor response [ Time Frame: Pre-treatment, week 5, week 11, and then every 12 weeks until off study ] [ Designated as safety issue: No ]

MRI scans of the brain and spine is obtained pre-treament, pre-consolidation, pre-maintenance, and then every 12 weeks on maintenance.

Enrollment:

19

Study Start Date:

August 2005

Primary Completion Date:

August 2010 (Final data collection date for primary outcome measure)

Intervention Details:

Drug: topotecan hydrochloride

Participants receive intraventricular topotecan, .2 mg, administered via an indwelling ventricular reservoir daily for 5 consecutive days during weeks 1 and 3 of the first four weeks of therapy (induction), during weeks 5 and 8 of the next 6 weeks of therapy (consolidation), and during weeks 11, 15, 19, 23, 27, 31, 35, 39, 43, 47, and 51 (maintenance therapy).

Other Name: Hycamptin

Detailed Description:

OBJECTIVES:

Primary

Determine the maximum tolerated dose (MTD) of intraventricular topotecan in young patients with neoplastic meningitis secondary to leukemia, lymphoma, or solid tumors.

Determine the toxic effects and dose-limiting toxicity of this drug in these patients.

Determine whether the MTD of this drug is also the pharmacokinetic optimal dose, defined by the topotecan lactone concentration in the cerebral spinal fluid (CSF), in these patients.

Secondary

Determine, preliminarily, the antitumor activity of this drug in these patients.

Determine the pharmacokinetics of this drug in the CSF of these patients.

Correlate observed effects of post-treatment central review imaging (if feasible) with response to this drug in these patients.

OUTLINE: This is a non-randomized, dose-escalation, multicenter study.

Cohorts of 3-6 patients receive escalating doses of intraventricular topotecan until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Once the MTD is determined, the cohort is expanded to 25 patients and the MTD is declared the pharmacokinetic optimal dose provided 23 of 25 patients treated at the MTD achieve the target pharmacokinetic parameter.

PROJECTED ACCRUAL: A total of 28-49 patients will be accrued for this study within 9-24 months.

More than 2 weeks since prior and no other concurrent investigational agents

No other concurrent intra-CSF or systemic therapy for leptomeningeal disease

Contacts and Locations

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Please refer to this study by its ClinicalTrials.gov identifier: NCT00112619